Immunohistochemical localization of transforming growth factor alpha in chemically induced rat hepatocellular carcinomas with reference to differentiation and proliferation

Hepatocellular carcinomas (HCCs) were induced in male Fischer 344 rats with dietary 3'-methyl-4-(dimethylamino)-azobenzene treatment and wet-e classif ied into solid, glandular (well- or poorly differentiated), and trabecular types. Investigation of cell proliferation kinetics and immunohistochemical localization of transforming growth factor alpha (TGF-alpha) demonstrated all solid (n = 24) and poorly differentiated glandular type (n = 6) HCCs to have TGF-alpha-positive nuclei. Nuclear staining of TGF-alpha was also obs erved In 13 of 28 (46%) trabecular-type HCCs, whereas 12 (43%) exhibited cy toplasmic staining, and 3 (11%) were negative. As for well-differentiated g landular HCCs, 7 of 20 (35%) were positively stained in their nucleus, anot her 7 (35%) demonstrated antibody binding in the cytoplasm, and 6 (30%) wer e negative. The order for growth rate evaluated by bromodeoxyuridine (BrdU) labeling was solid (38.22%). poorly differentiated glandular (26.82%), tra becular (7.98%), and well-differentiated glandular (2.57%) types. For trabe cular HCCs with nuclear, cytoplasmic, or negative TGF reactions, values wer e 13.39% (n = 13), 3.61% (n = 12), and 2.01% (n = 3), respectively. Likewis e, BrdU-labeling indices for the counterpart groups of well-differentiated glandular type HCCs were 4.53, 1.91, and 1.29%. respectively The results in dicate that TGF-alpha expression might be linked to histopathological diffe rentiation and cell proliferation in rat HCCs.